{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:11:27Z","timestamp":1793067087083,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2023-00238039"],"award-info":[{"award-number":["RS-2023-00238039"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Soonchunhyang University Research Fund","award":["RS-2023-00238039"],"award-info":[{"award-number":["RS-2023-00238039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic alcohol consumption induces oxidative stress not only in the liver but also in the gastrointestinal tract, where prolonged intestinal ethanol absorption plays a pivotal and underrecognized role. This review reframes ethanol pharmacokinetics to emphasize sustained jejunal and ileal uptake, which maintains elevated blood alcohol levels and perpetuates redox imbalance across the gut\u2013liver axis. We integrate recent findings on ethanol-induced barrier dysfunction, CYP2E1-mediated ROS production, microbial dysbiosis, and mitochondrial disruption, proposing that the intestine is an active site of injury and a driver of systemic inflammation. Key mechanistic insights reveal that gut-derived endotoxins, compromised epithelial integrity, and microbiome\u2013mitochondria interactions converge to exacerbate hepatic and extrahepatic damage. We further explore emerging therapeutic strategies\u2014ranging from NAD+ repletion and probiotics to fecal microbiota transplantation\u2014that target this upstream pathology. Recognizing prolonged intestinal ethanol absorption as a clinically meaningful phase offers new directions for early intervention and redox-based treatment in alcohol-associated disease.<\/jats:p>","DOI":"10.3390\/ijms26125442","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T06:11:08Z","timestamp":1749190268000},"page":"5442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Prolonged Intestinal Ethanol Absorption and Oxidative Stress: Revisiting the Gut\u2013Liver Axis in Alcohol-Associated Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3644-9120","authenticated-orcid":false,"given":"Beom Sun","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keungmo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology and Hepatology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihyun","family":"Park","sequence":"additional","affiliation":[{"name":"Forensic Chemistry Division, National Forensic Service, Wonju 26460, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.freeradbiomed.2007.11.004","article-title":"CYP2E1 and oxidative liver injury by alcohol","volume":"44","author":"Lu","year":"2008","journal-title":"Free Radic. 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